Metachronous Colorectal Cancer in Icelandic MSH6 and PMS2 Lynch Syndrome Carriers in 1955-2017 : A Population-based Study

Funding Information: Funding The study was partially funded by the Research Fund at Landspitali University Hospital. The funder had no role in the design of the study, collection, analysis, and interpretation of the data or in writing the manuscript.Peer reviewe

Vitamin D status and association with gestational diabetes mellitus in a pregnant cohort in Iceland.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadBackground: Vitamin D deficiency has been associated with an increased risk of gestational diabetes mellitus (GDM), one of the most common pregnancy complications. The vitamin D status has never previously been studied in pregnant women in Iceland. Objective: The aim of this research study was to evaluate the vitamin D status of an Icelandic cohort of pregnant women and the association between the vitamin D status and the GDM incidence. Design: Subjects included pregnant women (n = 938) who attended their first ultrasound appointment, during gestational weeks 11-14, between October 2017 and March 2018. The use of supplements containing vitamin D over the previous 3 months, height, pre-pregnancy weight, and social status were assessed using a questionnaire, and blood samples were drawn for analyzing the serum 25‑hydroxyvitamin D (25OHD) concentration. Information regarding the incidence of GDM later in pregnancy was collected from medical records. Results: The mean ± standard deviation of the serum 25OHD (S-25OHD) concentration in this cohort was 63±24 nmol/L. The proportion of women with an S-25OHD concentration of ≥ 50 nmol/L (which is considered adequate) was 70%, whereas 25% had concentrations between 30 and 49.9 nmol/L (insufficient) and 5% had concentrations < 30 nmol/L (deficient). The majority of women (n = 766, 82%) used supplements containing vitamin D on a daily basis. A gradual decrease in the proportion of women diagnosed with GDM was reported with increasing S-25OHD concentrations, going from 17.8% in the group with S-25OHD concentrations < 30 nmol/L to 12.8% in the group with S-25OHD concentrations ≥75 nmol/L; however, the association was not significant (P for trend = 0.11). Conclusion: Approximately one-third of this cohort had S-25OHD concentrations below adequate levels (< 50 nmol/L) during the first trimester of pregnancy, which may suggest that necessary action must be taken to increase their vitamin D levels. No clear association was observed between the vitamin D status and GDM in this study. Keywords: cod liver oil; gestational diabetes mellitus; nutritional status; pregnancy; supplements; vitamin D.University of Iceland Research Fund Science Fund of Landspitali National University Hospita

Keratinocytes secrete multiple inflammatory and immune biomarkers, which are regulated by LL‐37, in a psoriasis mimicking microenvironment

To access publisher's full text version of this article click on the hyperlink belowPsoriasis is an autoimmune disease driven by a Th17 response linked to the antimicrobial peptide (AMP) LL-37 that has been connected to the induction and chronicity of psoriasis. We show that keratinocytes secrete various immune biomarkers with a direct link to psoriasis immunopathogenesis. Under pro-inflammatory microenvironmental conditions, LL-37 was found to regulate keratinocyte secretion of various immune biomarkers (eg C-X-C motif chemokine ligand (CXCL)8 and interleukin (IL)-1 beta) and alter extracellular signal-regulated kinase (ERK)1/2 signalling. However, during neutral conditions LL-37 induced a different pattern of keratinocyte immune biomarker secretion (eg vascular endothelial growth factor, CXCL8 and IL-6). Thus, an interesting pattern emerged regarding the immunomodulatory effects of LL-37 on keratinocytes; in general, expression of immune biomarkers that were upregulated in a Th1-like microenvironment was downregulated in the presence of LL-37. In contrast, LL-37 reinforced the Th17 response. In active psoriatic skin lesions, LL-37 expression was found to be significantly upregulated, which was also evident from the unique diffuse epidermic expression pattern not found in healthy skin. Finally, successful phototherapy of psoriasis patients converted this LL-37 inflammatory psoriatic skin pattern into a more localized basal layer expression as found in healthy controls. Thus, these findings demonstrate that LL-37 has a significant role in skin immune homeostasis and that its interplay with keratinocytes may have a more direct role in the immunopathogenesis of psoriasis than previously thought.Icelandic Research Fund Landspitali University Hospital Research Fun

Follow-Up Genotoxic Study: Chromosome Damage Two and Six Years after Exposure to the Prestige Oil Spill.

BACKGROUND: The north-west coast of Spain was heavily contaminated by the Prestige oil spill, in 2002. Individuals who participated in the clean-up tasks showed increased chromosome damage two years after exposure. Long-term clinical implications of chromosome damage are still unknown. OBJECTIVE: To realize a follow-up genotoxic study to detect whether the chromosome damage persisted six years after exposure to the oil. DESIGN: Follow-up study. SETTING: Fishermen cooperatives in coastal villages. PARTICIPANTS: Local fishermen who were highly exposed (n = 52) and non-exposed (n = 23) to oil seven years after the spill. MEASUREMENTS: Chromosome damage in circulating lymphocytes. RESULTS: Chromosome damage in exposed individuals persists six years after oil exposure, with a similar incidence than those previously detected four years before. A surprising increase in chromosome damage in non-exposed individual was found six years after Prestige spill vs. those detected two years after the exposure. LIMITATIONS: The sample size and the possibility of some kind of selection bias should be considered. Genotoxic results cannot be extrapolated to the approximately 300,000 individuals who participated occasionally in clean-up tasks. CONCLUSION: The persistence of chromosome damage detected in exposed individuals six years after oil exposure seems to indicate that the cells of the bone marrow are affected. A surprising increase in chromosome damage in non-exposed individuals detected in the follow-up study suggests an indirect exposition of these individuals to some oil compounds or to other toxic agents during the last four years. More long-term studies are needed to confirm the presence of chromosome damage in exposed and non-exposed fishermen due to the association between increased chromosomal damage and increased risk of cancer. Understanding and detecting chromosome damage is important for detecting cancer in its early stages. The present work is the first follow-up cytogenetic study carried out in lymphocytes to determine genotoxic damage evolution between two and six years after oil exposure in same individuals.This study was provided by grants from the Health Institute Carlos III FEDER/ERDF (PI03/1685; PI07/0086), Sociedad Española de Neumología y Cirugía Torácica (SEPAR), Comissionat per a Universitats i Recerca from Generalitat de Catalunya (SGR14-903; FI-00312), Centro de Investigación en Red de Enfermedades Respiratorias and Universidad Autónoma de Barcelona (PS-456-01/08)

Follow-Up Genotoxic Study: Chromosome Damage Two and Six Years after Exposure to the Prestige Oil Spill.

BACKGROUND: The north-west coast of Spain was heavily contaminated by the Prestige oil spill, in 2002. Individuals who participated in the clean-up tasks showed increased chromosome damage two years after exposure. Long-term clinical implications of chromosome damage are still unknown. OBJECTIVE: To realize a follow-up genotoxic study to detect whether the chromosome damage persisted six years after exposure to the oil. DESIGN: Follow-up study. SETTING: Fishermen cooperatives in coastal villages. PARTICIPANTS: Local fishermen who were highly exposed (n = 52) and non-exposed (n = 23) to oil seven years after the spill. MEASUREMENTS: Chromosome damage in circulating lymphocytes. RESULTS: Chromosome damage in exposed individuals persists six years after oil exposure, with a similar incidence than those previously detected four years before. A surprising increase in chromosome damage in non-exposed individual was found six years after Prestige spill vs. those detected two years after the exposure. LIMITATIONS: The sample size and the possibility of some kind of selection bias should be considered. Genotoxic results cannot be extrapolated to the approximately 300,000 individuals who participated occasionally in clean-up tasks. CONCLUSION: The persistence of chromosome damage detected in exposed individuals six years after oil exposure seems to indicate that the cells of the bone marrow are affected. A surprising increase in chromosome damage in non-exposed individuals detected in the follow-up study suggests an indirect exposition of these individuals to some oil compounds or to other toxic agents during the last four years. More long-term studies are needed to confirm the presence of chromosome damage in exposed and non-exposed fishermen due to the association between increased chromosomal damage and increased risk of cancer. Understanding and detecting chromosome damage is important for detecting cancer in its early stages. The present work is the first follow-up cytogenetic study carried out in lymphocytes to determine genotoxic damage evolution between two and six years after oil exposure in same individuals.This study was provided by grants from the Health Institute Carlos III FEDER/ERDF (PI03/1685; PI07/0086), Sociedad Española de Neumología y Cirugía Torácica (SEPAR), Comissionat per a Universitats i Recerca from Generalitat de Catalunya (SGR14-903; FI-00312), Centro de Investigación en Red de Enfermedades Respiratorias and Universidad Autónoma de Barcelona (PS-456-01/08)

Persistence of breakage in specific chromosome bands 6 years after acute exposure to oil

Abstract BACKGROUND: The identification of breakpoints involved in chromosomal damage could help to detect genes involved in genetic disorders, most notably cancer. Until now, only one published study, carried out by our group, has identified chromosome bands affected by exposure to oil from an oil spill. In that study, which was performed two years after the initial oil exposure in individuals who had participated in clean-up tasks following the wreck of the Prestige, three chromosomal bands (2q21, 3q27, 5q31) were found to be especially prone to breakage. A recent follow-up study, performed on the same individuals, revealed that the genotoxic damage had persisted six years after oil exposure. OBJECTIVES: To determine whether there exist chromosome bands which are especially prone to breakages and to know if there is some correlation with those detected in the previous study. In addition, to investigate if the DNA repair problems detected previously persist in the present study. DESIGN: Follow-up study performed six years after the Prestige oil spill. SETTING: Fishermen cooperatives in coastal villages. PARTICIPANTS: Fishermen highly exposed to oil spill who participated in previous genotoxic study six years after the oil. MEASUREMENTS: Chromosome damage in peripheral lymphocytes. For accurate identification of the breakpoints involved in chromosome damage of circulating lymphocytes, a sequential stain/G-banding technique was employed. To determine the most break-prone chromosome bands, two statistical methods, the Fragile Site Multinomial and the chi-square tests (where the bands were corrected by their length) were used. To compare the chromosome lesions, structural chromosome alterations and gaps/breaks between two groups of individuals we used the GEE test which takes into account a possible within-individual correlation. Dysfunctions in DNA repair mechanisms, expressed as chromosome damage, were assessed in cultures with aphidicolin by the GEE test. RESULTS: Cytogenetic analyses were performed in 47 exposed individuals. A total of 251 breakpoints in exposed individuals) were identified, showing a non-uniform distribution in the human ideogram. Ten chromosome bands were found to be especially prone to breakage through both statistical methods. By comparing these bands with those observed in certain exposed individuals who had already participated the previous study, it was found in both studies that four bands (2q21, 3q27, 5q31 and 17p11.2) are particularly sensitive to breakage. Additionally, the dysfunction in DNA repair mechanisms was not significantly higher in oil-exposed individuals than in non-exposed individuals. LIMITATIONS: The sample size and the possibility of some kind of selection bias should be considered. Genotoxic results cannot be extrapolated to the high number of individuals who participated occasionally in clean-up tasks. CONCLUSION: Our findings show the existence of at least four target bands (2q21, 3q27, 5q31 and 17p11.2) with a greater propensity to break over time after an acute exposure to oil. The breaks in these bands, which are commonly involved in hematological cancer, may explain the increase of cancer risk reported in chronically benzene-exposed individuals. In addition, a more efficiency of the DNA repair mechanisms has been detected six years after in fishermen who were highly exposed to the oil spill. To date, only this study, performed by our group on the previous and present genotoxic effects, has analyzed the chromosomal regions affected by breakage after an acute oil exposure

Follow-Up Genotoxic Study: Chromosome Damage Two and Six Years after Exposure to the Prestige Oil Spill

BACKGROUND: The north-west coast of Spain was heavily contaminated by the Prestige oil spill, in 2002. Individuals who participated in the clean-up tasks showed increased chromosome damage two years after exposure. Long-term clinical implications of chromosome damage are still unknown. OBJECTIVE: To realize a follow-up genotoxic study to detect whether the chromosome damage persisted six years after exposure to the oil. DESIGN: Follow-up study. SETTING: Fishermen cooperatives in coastal villages. PARTICIPANTS: Local fishermen who were highly exposed (n = 52) and non-exposed (n = 23) to oil seven years after the spill. MEASUREMENTS: Chromosome damage in circulating lymphocytes. RESULTS: Chromosome damage in exposed individuals persists six years after oil exposure, with a similar incidence than those previously detected four years before. A surprising increase in chromosome damage in non-exposed individual was found six years after Prestige spill vs. those detected two years after the exposure. LIMITATIONS: The sample size and the possibility of some kind of selection bias should be considered. Genotoxic results cannot be extrapolated to the approximately 300,000 individuals who participated occasionally in clean-up tasks. CONCLUSION: The persistence of chromosome damage detected in exposed individuals six years after oil exposure seems to indicate that the cells of the bone marrow are affected. A surprising increase in chromosome damage in non-exposed individuals detected in the follow-up study suggests an indirect exposition of these individuals to some oil compounds or to other toxic agents during the last four years. More long-term studies are needed to confirm the presence of chromosome damage in exposed and non-exposed fishermen due to the association between increased chromosomal damage and increased risk of cancer. Understanding and detecting chromosome damage is important for detecting cancer in its early stages. The present work is the first follow-up cytogenetic study carried out in lymphocytes to determine genotoxic damage evolution between two and six years after oil exposure in same individuals

Chromosome damage in exposed and non-exposed individuals from P2y and P6y genotoxic studies and in control individuals.

<p>Chromosome damage in exposed and non-exposed individuals from P2y and P6y genotoxic studies and in control individuals.</p

Flow diagram of the study.

<p>^aDetailed description in Zock et al. 2007. ^bDetailed description in Rodriguez-Trigo et al. 2010.</p